Medicine in the Fourth Dimension

Cederroth, Christopher R.; Albrecht, Urs; Bass, Joseph; Brown, Steven A.; Dyhrfjeld-Johnsen, Jonas; Gachon, Frédéric; Green, Carla B.; Hastings, Michael H.; Helfrich‐Förster, Charlotte; Hogenesch, John B.; Lévi, Françis; Loudon, A. S. I.; Lundkvist, Gabriella B.; Meijer, Johanna H.; Rosbash, Michael; Takahashi, Joseph S.; Young, Michael W.; Canlon, Barbara

doi:10.1016/j.cmet.2019.06.019

Cited by 266 publications

(234 citation statements)

References 157 publications

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“…Interestingly Besides, our genetic alteration analysis also suggested the low mutation rates of these CCRGs in the risk-score model, which was also in line with the current view that CCRGs were evolutionarily conserved in eukaryotes (18).…”

Section: Discussionsupporting

confidence: 89%

Genetic Landscapes and Prognostic Implications of Circadian Rhythm in Non-small Cell Lung Cancer

Chen

Jiang

et al. 2020

Preprint

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Abstract Background: Circadian rhythm plays an influential role in the vast majority of behavior and physiology, even of tumorigenesis and development. In this study, we tried to explore the prognostic implication for non-small cell lung cancer (NSCLC) based on the expression profiles of circadian clock-related genes (CCRGs), and describe the changes of immune infiltration and cell functions of related to the circadian rhythm.Methods: Univariate and multivariate Cox proportional hazard regression were performed to determine and construct a CCRGs risk-score significantly correlated with overall survival (OS) of the training set and validation set. GO, KEGG, and GSVA indicated discrepant changes in cellular processes and signaling pathways associated with these CCRGs. Further, immune cell infiltration, mutation rates, and related drugs and pathways analyses were investigated by the online analysis platform and the algorithm provided by works of literature. Results: The risk-score based on ten-gene signatures could independently predict the OS both in TCGA lung adenocarcinoma (p < 0.0001, HR: 2.117, 95% CI: 1.546 to 2.900) and lung squamous cell carcinoma (p < 0.0001, HR: 2.066, 95% CI: 1.552 to 2.751), respectively. The risk-score also had superior accuracy and predictability (LUAD: AUC 0.788; LUSC: AUC 0.738). The prognostic performance of the ten-gene signature was finally validated in validation set based on GEO cohorts. The circadian oscillations driven by CCRGs could disturb the metabolism and cellular functions of cancer cells. We also found that the infiltration level of critical cells in specific anti-tumor immunity process was suppressed apparently. In contrast, the infiltrating of inflammatory cells and immune cells with negative regulatory effects were promoted in the high-risk group. CCRGs were evolutionarily conserved with low mutation rates, which brought difficulties to explore therapeutic targets. Conclusions: We described the landscapes and prognostic implications of CCRGs. The risk-score based on CCRGs was an independent predictor of prognosis and could significantly stratify patient outcomes and immune cell infiltration levels. CCRGs were evolutionarily conserved with low mutation rates, which brought difficulties to explore therapeutic targets.Our study revealed that circadian rhythms might play an influential role in the NSCLC.

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Section: Discussionsupporting

confidence: 89%

Genetic Landscapes and Prognostic Implications of Circadian Rhythm in Non-small Cell Lung Cancer

Chen

Jiang

et al. 2020

Preprint

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“…Besides, our genetic alteration analysis also suggested the low mutation rates of these CCRGs in the riskscore model, which was also in line with the current view that CCRGs were evolutionarily conserved in eukaryotes (18). Moreover, this conservatism would affect plenty of critical cell functions, such as immunomodulatory.…”

Section: Discussionsupporting

confidence: 88%

“…Circadian biology is being considered as the fourth dimension of modern medicine (18). There is clear evidence for the differential expression of CCRGs in a variety of diseases, and cancers are no exception (19).…”

Section: Discussionmentioning

confidence: 99%

Genetic Landscapes and Prognostic Implications of Circadian rhythm in Non-small Cell Lung Cancer

Chen

Tian

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Circadian rhythm plays an influential role in the vast majority of behavior and physiology, even of tumorigenesis and development. In this study, we tried to explore the prognostic implication for non-small cell lung cancer (NSCLC) based on the expression profiles of circadian clock-related genes (CCRGs), and describe the changes of immune infiltration and cell functions of related to the circadian rhythm.Methods: Univariate and multivariate Cox proportional hazard regression were performed to determine and construct a CCRGs risk-score significantly correlated with overall survival (OS) of the training set and validation set. GO, KEGG, and GSVA indicated discrepant changes in cellular processes and signaling pathways associated with these CCRGs. Further, immune cell infiltration, mutation rates, and related drugs and pathways analyses were investigated by the online analysis platform and the algorithm provided by works of literature. Results: The risk-score based on ten-gene signatures could independently predict the OS both in TCGA lung adenocarcinoma (p < 0.0001, HR: 2.117, 95% CI: 1.546 to 2.900) and lung squamous cell carcinoma (p < 0.0001, HR: 2.066, 95% CI: 1.552 to 2.751), respectively. The risk-score also had superior accuracy and predictability (LUAD: AUC 0.788; LUSC: AUC 0.738). The prognostic performance of the ten-gene signature was finally validated in validation set based on GEO cohorts. The circadian oscillations driven by CCRGs could disturb the metabolism and cellular functions of cancer cells. We also found that the infiltration level of critical cells in specific anti-tumor immunity process was suppressed apparently. In contrast, the infiltrating of inflammatory cells and immune cells with negative regulatory effects were promoted in the high-risk group. CCRGs were evolutionarily conserved with low mutation rates, which brought difficulties to explore therapeutic targets. Conclusions: We described the landscapes and prognostic implications of CCRGs. The risk-score based on CCRGs was an independent predictor of prognosis and could significantly stratify patient outcomes and immune cell infiltration levels. CCRGs were evolutionarily conserved with low mutation rates, which brought difficulties to explore therapeutic targets. Our study revealed that circadian rhythms might play an influential role in the NSCLC.

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“…The notion that circadian rhythm disruptions lead to an increased likelihood of mammary tumor development is supported by studies that female workers taking frequent night shifts have disrupted internal clocks and an increased risk of developing breast cancer (BC) (Davis et al, 2001;Schernhammer et al, 2001;Wegrzyn et al, 2017). It has been reported that circadian genes have anti-tumor roles in multiple cancer types (de Assis et al, Papagiannakopoulos et al, 2016;Tang et al, 2017) and may act as tumor suppressors by regulating a wide variety of pathophysiological events, including cellular metabolism and pathogenesis of cancer (Cederroth et al, 2019;Lesicka et al, 2018;Lin and Farkas, 2018). Indeed, disrupted circadian rhythm likely affects multiple hallmarks of cancer, including proliferative signaling maintenance, cell death resistance, replicative immortality, invasion and metastasis activation, and energy metabolism reconfiguration (Hanahan and Weinberg, 2011).…”

Section: Introductionmentioning

confidence: 99%

A Non-canonical Function of BMAL1 Metabolically Limits Obesity-Promoted Triple-Negative Breast Cancer

Ramos

Ouyang

et al. 2020

iScience

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Medicine in the Fourth Dimension

Cited by 266 publications

References 157 publications

Genetic Landscapes and Prognostic Implications of Circadian Rhythm in Non-small Cell Lung Cancer

Genetic Landscapes and Prognostic Implications of Circadian Rhythm in Non-small Cell Lung Cancer

Genetic Landscapes and Prognostic Implications of Circadian rhythm in Non-small Cell Lung Cancer

A Non-canonical Function of BMAL1 Metabolically Limits Obesity-Promoted Triple-Negative Breast Cancer

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